A Research Of The Relationship Between The Indoleamine2,3-Dioxygenase And Breast Cancer Angiogenesis

Objective:To evaluate the expression of the Indoleamine2,3-Dioxygenase and microvessel density in breast cancer tissue in patients of all clinical stages, and the relevance between them, attempting to provide more theory basis for the application of IDO relevant inhibitors in tumor immunotherapy.Methods:1. Using immunohistochemical method to detect the expression of IDO and micro vascular density (MVD) marked by CD105of65patients,to make sure the relevance of IDO and MVD. And using statistical methods to clear whether there is a correlation lying between the two indexes and the clinical pathological indexes.2. Distant metastasis of breast cancer in mice model was established. When the volume of tumor grow to1cm3, the15mice will be randomly divided into three groups, they were respectively given normal saline subcutaneously, given IDO’s backstair inhibitor JSI-124subcutaneously, given IDO’s direct inhibitor1-MT orally, the three processing lasted for10days. Observe and record the changes of body weight and tumor size in mice periods. After the last measurement of tumor volume, all the mice were killed and tumors and lung tissue were got, lung metastatic nodules were counted, and the mice tumors were detected by immunohistochemistry and western blot, using statistical methods to compare the differences between the microvascular density and IDO of the three groups lead by IDO inhibitor.Results:1. Immunohistochemistry showed that there were42cases were positive for expression of IDO, accounting for64.6%of all specimens; lymph node metastasis, TNM stage, histological grade had correlation with IDO and MVD-CD105(p<0.05), microvessel density in patients with different clinical stages or histological grade is different significantly (p<0.05), and a positive correlation was lying between the expression IDO and MVD-CD105(R2=0.452, p<0.05)2. Distant metastasis of breast cancer in mice model was successfully established, compared with NS control group1-MT treatment group and the tumor growth in mice JSI-124treatment group was obviously suppressed, tumor weight difference is remarkable, the anti-tumor rate of1-MT group of mice was43.1%, and the JSI-124group was14.8%. Western blotting results and immunohistochemistry results confirmed that MVD-CD105had significant differences with the expression of IDO and pulmonary metastasis nodule count (R2=0.845,0.724)Conclusion:1. There is an association between the micro vascular density marked by CD105and the expression of Indoleamine2,3-Dioxygenase. Indoleamine2,3-Dioxygenase has the potential to participate in or contribute to the formation of new capillaries, but the specific mechanism is unclear.2. Using Indoleamine2,3-Dioxygenase relevant inhibitors can reduce the formation of new blood vessels in distant metastasis of breast cancer mice model of, and reduce the possibility of tumor cells to distant metastases, These drugs may not only play a role in tumor microenvironment, they may inhibit tumor cell nutrition supply and reducing the possibility of hematogenous metastasis of the tumor cells.